• β Stard10 KO β-cells show altered granule morphology. • Deletion of Stard10 increased basal secretion of newly synthesised proinsulin. • β Stard10 KO islets had an altered lipidomics profile, including phosphatidylinositols. • STARD10 bound to phosphoinositides in a lipid overlay assay. • STARD10 structure reveals that its cavity readily accommodates phosphatidylinositols.