HCK (hematopoietic cell kinase) is a Src family non-receptor tyrosine kinase primarily expressed in myeloid cells and B lymphocytes that serves as a critical regulator of innate immune responses and cellular processes 1. The protein functions through multiple mechanisms including phosphorylation of downstream targets, regulation of autophagy flux via interactions with ATG2A and CBL, and activation of signaling pathways such as JAK-STAT 23. HCK promotes macrophage activation, phagocytosis, cell migration, actin cytoskeleton reorganization, and podosome formation while inhibiting autophagy in immune cells 12. Additionally, HCK regulates NLRP12-mediated PANoptosis, a form of programmed cell death important for innate immunity 4. Disease relevance includes roles in chr20 kidney disease where HCK promotes renal inflammation and fibrosis through macrophage activation 2, colorectal cancer development through adenoma initiation 3, and endometriosis progression via impaired macrophage phagocytosis 5. Clinical significance is highlighted by HCK's involvement in various malignancies including leukemia and solid tumors, making it an attractive therapeutic target 67. The kinase's role in HIV infection through Nef protein activation further underscores its therapeutic potential 7.