Based on limited published evidence, SEL1L2 functions as an adaptor subunit of the SYVN1 ubiquitin ligase complex involved in ER-associated degradation (ERAD). GO annotations localize SEL1L2 to the endoplasmic reticulum membrane, nuclear speck, and cilium. A de novo SEL1L2 truncation variant was identified in an NDD patient with trigonocephaly 1, suggesting potential involvement in neurodevelopmental disorders. Additionally, a DMR located between MACROD2/SEL1L2 genes showed association with BMI through gut microbiota-mediated epigenetic regulation 2, indicating possible metabolic relevance. However, direct functional characterization of SEL1L2 remains limited.