JAK1

Overview

JAK1 (Janus kinase 1) is a non-receptor tyrosine kinase that functions as a key signaling component downstream of multiple cytokine receptors. As part of the Janus kinase family, JAK1 helps transmit extracellular signals to intracellular pathways that regulate immune activation, inflammation, cell survival, proliferation, and differentiation. Because of this central role, JAK1 is an important biological node in immune-mediated disease and cancer biology.

In biomedical research and therapeutics, JAK1 is frequently studied as a drug target rather than as a structural protein alone. Selective JAK1 inhibition is used to modulate inflammatory signaling, and broader JAK1/2 inhibition has been investigated in interferon-driven disorders. Recent studies also suggest that altered JAK1 activity can influence tumor cell behavior, including cell-cycle progression, radioresistance, and cell death pathways. These findings place JAK1 at the intersection of immunology, dermatology, rare disease research, and oncology.

Focus of Latest Publications

Recent publications have focused on JAK1 as a therapeutic target across inflammatory disease, cancer, and interferon-mediated disorders. In atopic dermatitis, abrocitinib was highlighted as an oral JAK1 inhibitor with real-world interest in dose optimization, and a separate preclinical study explored a microneedle-based dual delivery platform combining JAK1 silencing by CRISPR-CasRx with EGCG-lactoferrin nanoparticles. In the mouse model of atopic dermatitis, this combined approach reduced dermatitis severity, epidermal thickening, mast cell infiltration, inflammatory cytokines, serum TSLP and IgE, and oxidative DNA damage, while suppressing JAK1 expression and activating the nuclear factor erythroid 2-related factor 2/HO-1 antioxidant pathway.

JAK1 inhibition was also reported in a clinical case of progressive alopecia areata arising during TNF-α inhibition, where improvement followed initiation of selective JAK1 inhibition after intralesional corticosteroid failure. In broader immune-mediated disease, a multicenter retrospective study evaluated JAK1/2 inhibitors, including baricitinib and ruxolitinib, in AGS gene-related interferonopathies. Treatment was associated with improvement in immunological and dermatological manifestations, but neurological benefit was limited and heterogeneous, with better responses in patients with milder phenotypes and earlier treatment initiation; adverse events were rare and mild.

In oncology, JAK1 emerged as a mechanistic node in hepatocellular carcinoma and head and neck squamous cell carcinoma. Saquinavir was shown to induce pyroptosis in HCC by targeting OTUD5, promoting ubiquitin-proteasome-mediated degradation of JAK1, and activating the caspase-3-GSDME axis; the drug also disrupted glucose metabolism and increased reactive oxygen species, and its combination with sorafenib showed synergistic antitumor activity. In HNSCC, CRISPR-Cas9 screening identified loss of JAK1 as a driver of radioresistance, with JAK1 knockout or abrocitinib delaying radiation-induced mitotic catastrophe, prolonging G2-M arrest, and reducing micronuclei formation; these effects were linked to reduced activation of polo-like kinase 1 and Aurora kinase A. The study further showed that KIF18A inhibition could counteract this protective cell-cycle arrest and enhance radiosensitivity.

Key Publications

NEWJun Treatment Trajectories and Dose Optimization of Abrocitinib in Moderate-to-Severe Atopic Dermatitis: A Real-World Landmark Analysis. (Clinical and experimental dermatology, 2026, PMID 42359476): "Abrocitinib is an effective oral Janus kinase 1 inhibitor for moderate-to-severe atopic dermatitis (AD), although real-world evidence regarding dose optimization strategies remains limited."
May Progressive alopecia areata during TNF-α inhibition with intralesional corticosteroid failure and subsequent improvement following JAK1 inhibition. (The Journal of dermatological treatment, 2026, PMID 42089250): "with subsequent improvement following initiation of selective Janus kinase 1 (JAK1) inhibition."
Jun Efficacy of JAK1/2 inhibitors in AGS genes-related interferonopathies: A multicenter retrospective observational study with treated vs untreated comparison. (Molecular genetics and metabolism, 2026, PMID 41871482): "This retrospective multicenter study analyzed the efficacy and safety of Janus kinase 1/2 (JAK1/2) inhibitors in 12 patients treated with Baricitinib or Ruxolitinib, compared with 20 untreated patients."
Apr Feasibility of combining JAK1 gene editing via CRISPR-CasRx with EGCG-lactoferrin nanoparticle therapy in a microneedle-based platform for atopic dermatitis. (Materials today. Bio, 2026, PMID 41685363): "...targets both oxidative stress and Janus kinase 1 (JAK1) expression, aiming for enhanced therapy of AD."
Apr Saquinavir induces pyroptosis through the OTUD5-JAK1-GSDME axis in hepatocellular carcinoma. (Free radical biology & medicine, 2026, PMID 41687749): "Additionally, SAQ potently targets the deubiquitinase OTUD5, accelerating the ubiquitin-proteasome mediated degradation of JAK1 and resulting in mitochondria disruption, which further activated the caspase-3-GSDME axis to induce pyroptosis."
May Loss of JAK1 Function Causes G2-M Cell-Cycle Defects Vulnerable to KIF18A Inhibition. (Cancer research, 2026, PMID 41591363): "the loss of JAK1 was identified as a driver of tumor cell radioresistance."