Here, we present evidence in β-cells and primary mouse and human islets which demonstrates that, following agonist binding and internalisation, endosomal GLP-1R binds to endoplasmic reticulum (ER)-localised ER-mitochondria membrane contact site (ERMCS) organising factor VAPB to engage SPHKAP, a PKA-RIα-specific A-kinase anchoring protein (AKAP) whose gene coding variants have previously been linked to T2D and high BMI risk in genome-wide association studies (GWAS). The gene discussed is SPHKAP; the disease is type 2 diabetes mellitus.