{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ALMS1 is a ubiquitously expressed protein whose dysfunction underlies Alström syndrome, a multisystem disorder characterized by retinal degeneration, sensorineural hearing loss, cardiomyopathy, metabolic disturbances, and progressive fibrosis. Studies have consistently shown that ALMS1 localizes to centrosomes, basal bodies, and the base of primary cilia, indicating a central role in ciliogenesis and maintenance of ciliary structure and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In addition to its ciliary functions, ALMS1 plays important roles in intracellular trafficking and centrosome cohesion. For instance, it has been implicated in the proper recruitment and stabilization of centrosomal proteins, which in turn influences microtubule organization and endosome recycling—a process crucial for the trafficking of key molecules such as GLUT4 in adipocytes and for maintaining tissue homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Moreover, ALMS1 deficiency has been linked to disrupted cell cycle regulation; recent work demonstrates that loss of ALMS1 impairs the normal postnatal cell cycle arrest of cardiomyocytes, predisposing to abnormal cardiac proliferation and dilated or restrictive cardiomyopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, perturbations in ALMS1-dependent pathways contribute to the metabolic defects observed in patients—including insulin resistance and obesity—as well as to sensory deficits in the retina and inner ear, where defects in ciliary structure correlate with impaired photoreceptor and hair cell function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, genetic studies have also associated ALMS1 variants with altered renal function, supporting a wider role for this gene in organ development and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gayle B Collin, Jan D Marshall, Akihiro Ikeda, et al. 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