LRP12 (LDL receptor-related protein 12) is a probable receptor involved in lipophilic molecule internalization and signal transduction, with emerging roles in neuromuscular and neoplastic disease. The protein localizes to clathrin-coated pits and the plasma membrane, consistent with endocytic function 1. LRP12 mutations cause oculopharyngodistal myopathy type 1 (OPDM1), characterized by progressive ocular, facial, pharyngeal, and distal limb weakness with pathological rimmed vacuoles and intranuclear inclusions 2. Disease-causing variants involve CGG repeat expansions in the 5'-untranslated region 3. Importantly, repeat length determines phenotypic switching: individuals with 61-100 repeats develop amyotrophic lateral sclerosis (ALS) with phosphorylated TDP-43 pathology in motor neurons, while those with 100-200 repeats present as OPDM 4. Both phenotypes feature RNA foci formation, though the underlying toxic mechanisms involve repeat length-dependent differences in RNA and protein gain-of-function 4. Beyond neuromuscular disease, LRP12 functions as a regulator of gastric cancer progression through AKT/mTOR signaling activation and M2 macrophage-mediated immunosuppression, suggesting a tumor-promoting role distinct from its classic receptor functions 5. LRP12 thus represents a multifunctional protein with context-dependent roles in neurodegenerative disease, myopathy, and cancer biology.