CHP1 (calcineurin-like EF-hand protein 1) is a multifunctional calcium-binding protein with roles in cellular homeostasis and protein quality control. Structurally, CHP1 contains EF-hand motifs enabling calcium-dependent conformational changes that regulate its interactions with partner proteins 1. Primary functions include: (1) Regulation of sodium-proton exchangers NHE1 and NHE3 at the plasma membrane, where CHP1 binding promotes their biosynthetic maturation, cell surface expression, and pH-sensitivity 23; (2) Stabilization and activation of glycerol-3-phosphate acyltransferases (GPAT3/4) essential for triacylglycerol synthesis and lipid droplet growth 4; (3) Cotranslational chaperoning of eukaryotic elongation factor 1A (eEF1A) biogenesis at the ribosome, preventing proteolysis and protein aggregation 5; (4) Negative regulation of calcineurin phosphatase activity, thereby inhibiting endocytosis and NFAT signaling. Disease relevance: CHP1 mutations cause autosomal recessive spastic ataxia 9. CHP1 reduction ameliorates spinal muscular atrophy (SMA) pathology by restoring calcineurin activity and endocytosis 6. In clear cell renal cell carcinoma, CHP1 downregulation is a novel feature of malignant progression, with high CHP1 expression correlating with improved prognosis 7. These findings establish CHP1 as a critical integrator of calcium signaling, metabolic regulation, and proteostasis with implications for neurological and metabolic disease therapeutics.