Hsh2d, short for haematopoietic SH2 domain containing, may play a role in multiple biological processes. It has been implicated in immune-related pathways as genes like Hsh2d have been associated with inflammatory/immune-related biological processes in lung macrophages [3]. Also, its expression was found to be related to interferon signaling-associated genes in doxorubicin-surviving proliferative cells [2].

In acute lymphoblastic leukaemia, Hsh2d was shown to contribute to methotrexate resistance in human T-cell acute lymphoblastic leukaemia. Downregulation of Hsh2d was observed in T-ALL compared with B-cell ALL. Overexpression of Hsh2d inhibited CD28-mediated IL-2 activation, and it was necessary for HuT-78 cells to be resistant to methotrexate [1].

In cervical squamous cell carcinoma, Hsh2d was part of an immune-based mRNA-lncRNA signature identified to predict overall survival [5].

In addition, in murine experimental colitis, the immune process-related factor Hsh2d was upregulated in colon tissues of macrophages with p38α deficiency, which ameliorated the colitis [4].

In summary, Hsh2d appears to have important functions in immune-related responses and disease resistance. Its role in conferring drug resistance in T-cell acute lymphoblastic leukaemia and its association with immune-based signatures in cervical squamous cell carcinoma highlight its significance in these disease areas. Also, its involvement in murine colitis through immune-related processes further emphasizes its importance in understanding disease mechanisms [1,4,5].