RILPL1 is a Rab-interacting protein that regulates cellular processes including ciliogenesis and centrosome homeostasis. Mechanistically, RILPL1 functions as a phospho-Rab-specific effector protein that binds to LRRK2-phosphorylated RAB10 and RAB12, leading to inhibition of primary ciliogenesis and defects in centrosomal cohesion 12. Additionally, RILPL1 participates in lysosomal trafficking by promoting Rab-mediated degradation of recycling endosomes, thereby restricting angiogenesis 3. RILPL1 disease relevance is established through GGC repeat expansions in its promoter region, which cause oculopharyngodistal myopathy type 4 (OPDM4), an adult-onset neuromuscular disorder characterized by progressive ocular, pharyngeal, and distal muscle weakness with pathological rimmed vacuoles 45. The pathogenic mechanism involves both RNA toxicity from repeat-containing transcripts that form nuclear foci and epigenetic hypermethylation silencing the expanded allele 4. Clinically, long-read sequencing technologies have improved diagnostic rates for RILPL1-associated OPDM by detecting these difficult-to-sequence repeat expansions 6. Understanding RILPL1's role in LRRK2 signaling also has implications for Parkinson's disease research, as pathogenic LRRK2 mutations dysregulate this pathway 7.