GNAI1 (G protein subunit alpha i1) is a key component of heterotrimeric G proteins that transduce signals downstream of G protein-coupled receptors (GPCRs) 1. The protein functions as a molecular switch, alternating between inactive GDP-bound and active GTP-bound states 1. GPCR activation promotes GDP release and GTP binding to GNAI1, which then interacts with effector proteins such as adenylate cyclase inhibitors (ADCY1, ADCY5, ADCY6), reducing intracellular cAMP levels 2. GNAI1's intrinsic GTPase activity hydrolyzes bound GTP to GDP, terminating signaling 1. Structurally, GNAI1 functions as an intracellular pH sensor; physiological pH variations alter the protein's structure and stability through electrostatic interactions within Switch regions, affecting agonist-mediated Gβγ release 3. Beyond classical GPCR signaling, GNAI1 plays roles in cell division, required for cortical dynein-dynactin complex recruitment during metaphase and normal cytokinesis 4. Clinically, GNAI1 dysregulation associates with colorectal cancer development and metastasis; downregulation of GNAI1 by exosomal miR-320d promotes angiogenesis via JAK2/STAT3 activation 5. GNAI1 loss also reduces colitis-associated tumorigenesis, with low expression correlating with decreased relapse-free survival in colorectal cancer patients 6. Additionally, GNAI1 mediates neuroprotection against ischemia-reperfusion injury through Akt signaling activation 7, and mutations in GNAI1 cause pediatric encephalopathies with deficient GTP binding and hydrolysis 8.