RPGRIP1L is a ciliary transition zone protein that functions as a negative regulator of thromboxane A2 receptor (TBXA2R) signaling 1 and plays critical roles in ciliary organization and planar cell polarity. The protein localizes to the ciliary basal body and transition zone, where it interacts with nephrocystin proteins (NPHP4 and NPHP6) to regulate apical junction organization 2. RPGRIP1L is essential for proper hypothalamic neuron development, particularly for POMC neuron specification; mutations correlate with increased food intake and obesity through altered arcuate nucleus development 3. Pathogenic RPGRIP1L variants cause severe ciliopathies including Joubert syndrome (JS type B), characterized by cerebellar-brainstem malformations, and often associated with renal involvement (nephronophthisis) and retinal dystrophy requiring close monitoring 45. RPGRIP1L mutations also cause Meckel syndrome and COACH syndrome, demonstrating multi-organ developmental effects 2. Additionally, RPGRIP1L functions as a candidate tumor suppressor gene; its downregulation occurs in 35% of hepatocellular carcinomas, and overexpression suppresses tumor cell colony formation through mitotic checkpoint regulation 6. The T615P missense mutation represents the most common RPGRIP1L disease variant in JS type B patients 5.