PSD2 (pleckstrin and Sec7 domain containing 2) is a multifunctional protein involved in membrane dynamics and cellular transport processes. The protein contains guanyl-nucleotide exchange factor activity and localizes to specialized membrane structures including cleavage furrows and ruffle membranes 1. In the context of phospholipid metabolism, PSD2 appears to function as a phosphatidylserine decarboxylase, converting phosphatidylserine to phosphatidylethanolamine, which is critical for maintaining plasma membrane fluidity and cellular drug susceptibilities 2. This enzymatic function directly impacts membrane physical properties, with PSD2 deletion resulting in altered membrane fluidity and phase transition temperatures 2. Recent genetic studies have identified PSD2 as a candidate risk gene for both early-onset and late-onset Alzheimer's disease, with rare missense variants showing significant associations (P = 2.05 × 10⁻⁶ for EOAD; P = 6.22 × 10⁻⁶ for LOAD) 3. The protein's involvement in endolysosomal transport processes suggests a potential mechanistic link to neurodegeneration 3. Additionally, PSD2 has been implicated in Parkinson's disease genetics as a candidate autosomal recessive gene 4, and its dysregulation has been observed in Alzheimer's disease brain tissue lipidomics studies 5.