biostudies-literatureUnknown11(1)Watanabe KIldr2 was initially identified as a genetic modifier of diabetes susceptibility in B6.DBA Lep^ob congenic mice, and was associated with decreased β-cell replication rates, reduced β-cell mass, and persistent mild hypoinsulinemic hyperglycemia. However, the molecular mechanisms of how the ILDR2 protein is involved in these effects are largely unknown. We sought to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underpinning ILDR2 function in pancreatic β-cells. Using TAP tag technology, we purified proteins interacting with ILDR2 in the pancreatic β-cell line MIN6, and identified the endoplasmic reticulum resident chaperones, GRP78 and PDIA1, as novel proteins interacting with ILDR2. We demonstrated that GRP78 interacted with ILDR2 and was possiblScientific reports8414https://www.ebi.ac.uk/biostudies/studies/S-EPMC8052334biostudies-literatureILDR2 stabilization is regulated by its interaction with GRP78.PMC8052334Matsumoto ATsuda HOhta SWatanabe KNakayama KIwamoto SfalseILDR2 stabilization is regulated by its interaction with GRP78.Ildr2 was initially identified as a genetic modifier of diabetes susceptibility in B6.DBA Lep^ob congenic mice, and was associated with decreased β-cell replication rates, reduced β-cell mass, and persistent mild hypoinsulinemic hyperglycemia. However, the molecular mechanisms of how the ILDR2 protein is involved in these effects are largely unknown. We sought to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underpinning ILDR2 function in pancreatic β-cells. Using TAP tag technology, we purified proteins interacting with ILDR2 in the pancreatic β-cell line MIN6, and identified the endoplasmic reticulum resident chaperones, GRP78 and PDIA1, as novel proteins interacting with ILDR2. We demonstrated that GRP78 interacted with ILDR2 and was possibl2021-01-01T00:00:00Z2021 Apr2025-04-04T14:35:46.572Z2022-02-09T15:51:49.914ZS-EPMC80523343386397810.1038/s41598-021-87884-7