SGK3 is a serine/threonine kinase that regulates ion channels, membrane transporters, and cellular signaling pathways with emerging roles in disease pathogenesis. Primary function: SGK3 phosphorylates and activates multiple ion channels (ENAC, KCNQ1, TRPV5/6) and nutrient transporters (NHE3, SLC34A2), regulating sodium, potassium, calcium, and phosphate homeostasis [UniProt]. Mechanism: SGK3 operates as a downstream effector of PI3K signaling, enabling AKT-independent mTORC1 activation and transcriptional reprogramming through phosphorylation of chr8 remodeling factors like BRG1 and transcription factors including STAT3 12. Disease relevance: SGK3 promotes vascular calcification in chr8 kidney disease by enhancing Pit-1 phosphate transporter expression and activity in vascular smooth muscle cells 3. In cancer, SGK3 drives estrogen receptor-positive breast cancer proliferation through STAT3/ZMIZ2-mediated β-catenin stabilization 4 and enables drug-tolerant persister survival following HER2 tyrosine kinase inhibitor exposure 1. SGK3 also sustains oncogenic signaling in PIK3CA-mutant colorectal tumors and regulates glucocorticoid-induced adipogenesis through chr8 remodeling 52. Clinical significance: SGK3 inhibition or genetic ablation shows promise in preventing obesity, vascular complications, and treatment resistance in hormone-driven cancers, positioning it as a therapeutic target across multiple disease contexts.