SERF2 (small EDRK-rich factor 2) is a 59-amino acid, highly charged protein that functions as a cellular driver of protein amyloid formation and aggregation 1. The protein promotes amyloid aggregation through charge complementation, specifically interacting with negatively charged and hydrophobic segments in aggregation-prone proteins 2. SERF2 contains three α-helical segments forming a UBA-like domain that can bind mono- and di-ubiquitin, potentially preventing proteasomal degradation of ubiquitinated proteins and thus promoting protein aggregation 3. Additionally, SERF2 specifically binds RNA G-quadruplexes and plays an important role in stress granule formation through liquid-liquid phase transitions 4. The protein shows pleiotropic functions in embryonic development, as Serf2 knockout mice exhibit delayed embryonic development and perinatal lethality 5. In disease contexts, SERF2 promotes amyloid formation in neuroblastoma cells, and its depletion alters amyloid deposit structure in mouse brain models 35. These findings establish SERF2 as a key cellular modifier of proteotoxicity with potential therapeutic relevance for neurodegenerative diseases characterized by protein aggregation, including Alzheimer's and Parkinson's disease 1.