Protein O-mannosylation: one sugar, several pathways, many functions.

Recent research has unveiled numerous important functions of protein glycosylation in development, homeostasis, and diseases. A type of glycosylation taking center stage is protein O-mannosylation (POM), a posttranslational modification conserved in a wide range of organisms, from yeast to humans. In animals, POM plays a crucial role in the nervous system, while POM defects cause severe neurological abnormalities and congenital muscular dystrophies. However, the molecular and cellular mechanisms underlying POM functions and biosynthesis remain not well understood. This review outlines recent studies on POM while focusing on the functions in the nervous system, summarizes the current knowledge about POM biosynthesis, and discusses the pathologies associated with POM defects. The evolutionary perspective revealed by studies in the Drosophila model system are also highlighted. Finally, the review touches upon important knowledge gaps in the field and discusses critical questions for future research on the molecular and cellular mechanisms associated with POM functions.