INSRR (insulin receptor-related receptor) is a transmembrane receptor tyrosine kinase that functions as a pH sensor activated by increased extracellular alkaline pH 1. The receptor autophosphorylates under alkaline conditions (pH > 7.9) and activates intracellular signaling pathways involving IRS1 and AKT1/PKB. INSRR is expressed in renal β-intercalated cells where it plays a critical role in acid-base homeostasis by regulating urinary bicarbonate secretion in response to alkali loading 1. Knockout of the insrr gene impairs bicarbonate secretion and alters expression of genes involved in ATP metabolism and electron transport chains 1. Beyond renal function, INSRR is implicated in broader physiological processes. The insulin receptor family regulates metabolism and longevity through mechanisms analogous to caloric restriction 2. In cancer contexts, INSRR has been identified as an immune-related biomarker in glioblastoma tumor microenvironment, correlating with immune cell infiltration including dendritic cells and T cells 3. Aberrant INSRR expression and promoter methylation have been observed in renal cell carcinoma and bladder cancer 45, suggesting potential roles in cancer biology. Additionally, INSRR variants have been examined as candidate susceptibility factors for type-2 diabetes, though no definitive associations were identified in Pima Indians 6.