Next, we investigated the effect of UPF2 deficiency on the viability and insulin secretion of β cells because (i) UPF3A and UPF3B are involved in regulating UPF2, a key core NMD activator in mammalian cells (25, 26) by sequestering away from and bridging the exon-junction complex (EJC) with UPF1 and UPF2, respectively, leading to the NMD activation (23), and genome-wide association (GWAS) data reveal that the UPF2 variant rs145580445 is significantly associated with type 2 diabetes risk (7). This evidence concerns the gene UPF1 and type 2 diabetes mellitus.