Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk . The risk alleles impair glucose - induced insulin secretion and , paradoxically but characteristically , are associated with decreased proinsulin :insulin ratios, indicating improved proinsulin conversion . Neither the identity of the causal variants, nor the gene(s) through which risk is conferred, have been firmly established . Whereas ARAP1 encodes a GTPase a ctivating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR) - related lipid transfer protein family. By integrating genetic fine - mapping and epigenomic annotation data, and performing promoter - reporter and chromatin conformational capture (3C) studies in ?? - cell lines, we localise the causal variant (s) at this locus to a 5Kb region which overlaps a stretch - enhancer active in islets . This region contain s several highly correlated T2D - risk variants , includi ng the rs140130268 indel . Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D - risk allele carriers display ed reduced levels of STARD10 mRNA , with no concomitant c hange in A RAP 1 mRNA levels. Correspondingly, ?? - cell - selective deletion of StarD10 in mice led to impaired glucose - stimulated Ca 2+ dynamics and insulin secretion , and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal . Conversely, over - expression of S tarD10 in the adult ?? - cell improved glucose tolerance in high fat - fed animals . In contrast, manipulation of Arap1 in ?? - cells had no impact on insulin secretion or proinsulin conversion in mice . This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in S TAR D 10 expression in the ?? - cell.