Moving forward, the successful repurposing of CCBs will depend on addressing key limitations: (1) optimizing blood–brain barrier penetration and tissue selectivity to enhance CNS efficacy while minimizing peripheral adverse effects; (2) elucidating pharmacogenetic predictors of response to enable precision medicine approaches; and (3) prioritizing combinatorial strategies, such as pairing CCBs with CGRP inhibitors in migraine or Nav1.7 blockers in neuropathic pain. Here, SCN9A is linked to migraine disorder.