Recombinant Human WDR45 protein

WDR45. also known as WIPI4. is a member of the WD40 repeat-containing protein family that plays a critical role in autophagy, a conserved cellular degradation pathway. This protein is encoded by the WDR45 gene located on the X chromosome and functions as a β-propeller scaffold to mediate protein-protein interactions. Structurally, it contains seven WD40 repeats that form a circular platform for binding partner molecules, particularly in autophagosome formation and lysosomal degradation processes.

Mutations in WDR45 are linked to neurodegenerative disorders such as beta-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA). BPAN is characterized by iron deposition in the basal ganglia, leading to progressive motor impairments, cognitive decline, and seizures. The pathogenic variants in WDR45 disrupt autophagy flux, resulting in defective clearance of protein aggregates and damaged organelles, which contributes to neuronal toxicity.

Recombinant WDR45 protein is engineered using expression systems (e.g., E. coli, mammalian cells) to study its molecular interactions, structural dynamics, and disease mechanisms. It serves as a vital tool for in vitro assays, including binding studies with phospholipids (e.g., PI3P) or autophagy-related proteins (e.g as ATG2A/B), as well as cellular rescue experiments in WDR45-deficient models. Researchers also utilize it to screen potential therapeutic compounds targeting autophagy dysregulation in BPAN and related disorders. Despite progress, challenges remain in understanding its post-translational modifications and tissue-specific regulatory networks. Current studies focus on elucidating its role in neural development and iron metabolism, aiming to bridge gaps between autophagy defects and neurodegeneration.