MON2 is a regulator of endosome-to-Golgi membrane trafficking that plays a critical role in retrograde transport and cargo sorting. Mechanistically, MON2 functions as part of a conserved complex with DOPEY proteins and ATP9A to mediate SNX3-retromer-dependent endosomal sorting 1. MON2 binds phosphatidic acid and localizes to the Golgi, endolysosomes, and endoplasmic reticulum exit sites, where it recruits kinesin-1 motor proteins for microtubule-dependent transport 2. The MON2-DOPEY complex drives separation of recycling endosomes from early endosomes and is specifically required for Wntless transport to the Golgi, preventing its lysosomal degradation 3. Beyond membrane trafficking, MON2 has emerged as a novel immune-oncology target with therapeutic potential, as it was identified in CRISPR screening studies as a regulator of tumor-immune interactions affecting response to immunotherapy 4. Additionally, rare coding variants in MON2 have been associated with neuroticism in large-scale exome sequencing studies 5. MON2 demonstrates clinical significance in cardiovascular disease, where abnormal monocyte subset Mon2 (CD14++CD16+CCR2+) characteristics independently predict poor outcomes following myocardial infarction and correlate with microvascular endothelial dysfunction 67. Novel MON2 gene fusions have also been identified in diagnostically challenging head and neck carcinomas 8.