C2CD4B encodes a calcium-dependent domain-containing protein that plays multiple roles in glucose homeostasis and vascular function. The gene is strongly associated with type 2 diabetes risk and glucose regulation 12. Variants in the C2CD4B locus are linked to reduced glucose-stimulated beta cell function, with carriers showing decreased insulin release in response to glucose 3. The protein acts as a transcriptional regulator, with a risk allele variant increasing enhancer activity and C2CD4B expression in pancreatic islets, particularly under inflammatory conditions 4. Mouse studies reveal sexually dimorphic metabolic effects, with C2cd4b knockout females showing impaired glucose tolerance and defective insulin secretion, while males exhibit increased body weight and fasting glucose on high-fat diets 5. In vascular biology, C2CD4B induces endothelial dysfunction through a PI3K/Akt/PKCα signaling pathway, promoting oxidative stress and reducing nitric oxide bioavailability 6. The protein also regulates inflammatory responses in retinal endothelium by modulating ICAM-1 expression and leukocyte binding 7. Additionally, C2CD4B expression is upregulated in colorectal tumors and contributes to a prognostic signature in rectal cancer 8.