In a multi-omics study, Wang et al [52] identified two functionally distinct beta cell subtypes: beta1, governed by HNF1A, HNF4A and HNF4G; and beta2, governed by TCF4, NEUROD1 and NFIA. Although beta2 cells showed higher exocytotic capacity and increased abundance in type 2 diabetes, the secretory capacity was impaired in both subtypes. The gene discussed is TCF4; the disease is type 2 diabetes mellitus.