WD repeat–containing protein 44 (WDR44)

WD repeat–containing protein 44 is a cytosolic scaffolding protein containing multiple WD40-repeat motifs, which fold into a seven-bladed β-propeller structure at its C-terminus. It serves as a specific effector for the small GTPase Rab11, binding preferentially to Rab11-GTP via its N-terminal Rab11-binding domain. WDR44 regulates membrane trafficking, notably endosome recycling, and negatively regulates ciliogenesis by competing with other Rab11 effectors (e.g., FIP3, Rabin8) for Rab11 interaction. Phosphorylation of WDR44 (by Akt or Sgk3) increases its affinity for Rab11, fine-tuning trafficking events. Pathogenic variants of WDR44 disrupt these processes, leading to ciliopathy-related syndromes. WDR44 also mediates export of newly synthesized proteins (such as E-cadherin, matrix metalloproteinases, and CFTR) from the ER to the plasma membrane through Rab-dependent pathways. Researchers have highlighted its essential role in ciliogenesis regulation and membrane trafficking, but it is not currently a therapeutic target.

Other names

WD repeat domain 44RPH11Rab11BPDKFZp686L20145SYM-4Rab11-binding proteinRabphilin-11