SIRPG (signal regulatory protein gamma) is a primate-specific type 1 transmembrane protein predominantly expressed in T cells that functions as an immunoglobulin-like cell surface receptor 1. The protein contains a short cytoplasmic domain without known signaling motifs and binds to CD47 to mediate cell-cell adhesion, though some functions appear CD47-independent 1. SIRPG plays a crucial role in T cell activation and proliferation, with enhanced expression following anti-CD3 stimulation and upregulation of mitosis-regulating genes like UBE2C and TOP2A 1. In cancer contexts, high SIRPG expression correlates with an inflamed tumor microenvironment characterized by increased T cells, B cells, NK cells, and M1 macrophages, and predicts favorable response to PD-1 blockade therapy 2. SIRPγ-expressing cancer stem-like cells promote immune escape through Hippo/YAP signaling, facilitating CD47 expression and inhibiting tumor cell phagocytosis 3. Genetic polymorphisms in SIRPG, particularly rs2281808, are associated with autoimmune diseases including type 1 diabetes and narcolepsy 45. The TT variant reduces SIRPγ expression and creates a heightened effector state in CD8 T cells with lower activation thresholds 4. SIRPG serves as a marker for GzmK-expressing CD8+ T cells and exhibits near mutually exclusive expression with GzmB in resting peripheral CD8+ T cells 1.