SH3KBP1 is an X-linked adapter protein that regulates multiple signaling pathways critical for immune function, muscle integrity, and cell survival. Functionally, SH3KBP1 enhances innate immune responses by promoting RIG-I polyubiquitination through TRIM25 interaction, thereby increasing interferon production 1. In skeletal muscle, SH3KBP1 binds dynamin-2 via its N-terminus and associates with the endoplasmic reticulum through calnexin, controlling myonuclei positioning and myofiber formation 2. The protein also recruits PI3K via liquid-liquid phase separation at bleb membranes through a Septin-SH3KBP1-PI3K axis, promoting anoikis resistance in detached cells 3. Additionally, SH3KBP1 functions as part of a SH3-domain-dependent adaptor module (CASS group) at podosomes and phagocytic cups in immune cells 4. Clinically, SH3KBP1 is implicated in autism spectrum disorder (ASD), identified as an associated gene in X-chrX-wide association studies 5. Loss of Sh3kbp1 increases susceptibility to viral infection and exacerbates centronuclear myopathy phenotypes 12. SH3KBP1 also serves as a predictive biomarker in infantile hemangioma pathogenesis and influences immunotherapy response and prognosis in epithelial ovarian carcinoma 67.