 Abstract RNA binding proteins, RBPs, which contain low-sequence complexity domains, can mediate the formation of cellular condensates and membrane-less organelles via liquid-liquid phase separation, LLPS. These proteins are also associated with the pathogenesis of a myotrophic lateral sclerosis, ALS, and their aggregation has been linked to the disease's progression. Recent research suggests that certain post-translational modifications, PTMs, may be responsible for the phase transition of these proteins, leading to the formation of insoluble aggregates. This review provides an overview of the key molecular mechanisms of LLPS-mediated aggregate formation by PTMs, which could lead to further understanding of the pathogenesis and development of ALS therapeutics. This article was authored by Huyeng Zhenchui, Jiyun Li, and Kiyun Kim.