ALMS1 is a ~0.5 megadalton protein localized to the base of centrioles that functions as a centrosome and basal body-associated protein with both ciliary and extra-ciliary roles 1. The protein is involved in PCM1-dependent intracellular transport and is required for proper formation and maintenance of primary cilia, microtubule-based sensory organelles 1. ALMS1 regulates multiple cellular processes including endosomal trafficking, actin organization, centrosome cohesion maintenance, and transcription 1, with recent evidence indicating critical functions in the hypothalamic-adipose axis. Loss of ALMS1 function in mesenchymal stem cells and adipose tissue is sufficient to cause insulin resistance, fatty liver disease, and dyslipidemia, suggesting ALMS1 is essential for proper adipose tissue expandability 2. Additionally, ALMS1 plays an early regulatory role in leptin-mediated hormonal control of metabolism 3. Biallelic mutations in ALMS1 cause Alström syndrome, a ciliopathy characterized by metabolic dysfunction, cone-rod retinal dystrophy, sensorineural hearing loss, dilated cardiomyopathy, obesity with disproportionate insulin-resistant diabetes, and progressive multi-organ fibrosis 1 4. The complex pathophysiology involves both ciliary dysfunction and mesenchyme-intrinsic metabolic defects 2. Most Alström syndrome patients have life expectancy rarely exceeding 40 years 4, and early diagnosis with intervention can improve outcomes 4.