Vps37d, a gene involved in the ESCRT-I complex, plays crucial roles in the machinery responsible for multivesicular body formation and exosome biogenesis [2]. The ESCRT complex is associated with immune-related functions and transport signaling pathways in various tumor cells [4]. Additionally, vacuolar protein sorting, in which Vps37d is involved, is important for the traffic of molecules between cellular organelles [3].

In a disabled boy with a chromoanagenesis-driven ultra-complex t(5;7;21)dn, the Vps37d gene from der(7) was disrupted by breakpoint junctions. Although multiple genes cooperate in normal neuronal development, the disruption of TRIO most likely caused the patient's MRD44-like phenotype, but the disruption of Vps37d may also have contributed as it is involved in key biological processes for neuronal development [1]. In patients with keratoconus, the gene encoding Vps37D from the ESCRT-I complex was found to be underexpressed at the mRNA level, suggesting disruptions in the exosome synthesis machinery [2]. In gastric and colorectal cancers with high microsatellite instability, frameshift mutations of Vps37d were observed, suggesting that these alterations might contribute to cancer development by deregulating vacuolar protein sorting proteins [3]. Pan-cancer analysis has shown that the ESCRT family gene Vps37D has significant variation in breast cancer, predicting patient prognosis and being related to the tumor microenvironment, highlighting its importance in breast cancer initiation, progression, and immune response [4].

In conclusion, Vps37d is essential for multivesicular body formation and exosome biogenesis, and is involved in important cellular processes such as vacuolar protein sorting. Its disruption or abnormal expression is associated with various diseases including neurodevelopmental disorders, keratoconus, and certain cancers. Studies on Vps37d contribute to understanding the mechanisms of these diseases and may provide potential targets for diagnosis and treatment.