Jak1, short for Janus kinase 1, is a cytoplasmic tyrosine kinase that is constitutively bound to several cytokine receptors. It plays a crucial role in phosphorylating downstream signal transducers and activators of transcription (STAT), thus being essential in the JAK-STAT signaling pathway. This pathway is involved in various biological processes such as cell growth, differentiation, and immune response [6].

In inflammatory bowel disease (IBD), JAK1 inhibitors like tofacitinib are being used and investigated for induction and maintenance of ulcerative colitis, highlighting the role of JAK1 in IBD pathogenesis [1,4]. In colorectal cancer, METTL3 promotes cancer progression by activating the JAK1/STAT3 signaling pathway. METTL3 enhances JAK1 translation and STAT3 transcription, leading to increased activation of p-STAT3 and upregulation of downstream effectors [2]. In renal cell carcinoma, EHBP1L1 binds and stabilizes JAK1, driving immune evasion. Depletion of EHBP1L1 inhibits tumor growth by enhancing CD8+ T-cell-mediated antitumor immunity [3]. JAK1 also promotes hepatitis D virus (HDV) replication, and its inhibition modulates ERK1/2 activation and S-HDAg phosphorylation, making it a potential antiviral target [5].

In conclusion, Jak1 is central to the JAK-STAT signaling pathway and is involved in multiple biological processes and disease conditions. Studies using various models, though not specifically KO/CKO mouse models in the provided references, have revealed its significance in IBD, colorectal cancer, renal cell carcinoma, and HDV infection, providing potential therapeutic targets for these diseases.