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However, advances in structural biology, chemical biology, and computational methodologies are rapidly expanding the scope of tractable therapeutic space. Emerging modalities, including targeted protein degradation, molecular glues, macrocycles, RNA\u2010targeting small molecules, covalent ligands, and artificial intelligence\u2010assisted molecular design, enable pharmacological mechanisms beyond classical occupancy\u2010based inhibition through strategies such as induced proximity, expanded molecular recognition, covalent engagement, and RNA\u2010level regulation. These approaches challenge the traditional binary classification of druggability and support a more context\u2010dependent view of therapeutic accessibility. Despite this progress, significant challenges remain in optimizing pharmacokinetic properties, ensuring selectivity, minimizing toxicity, and achieving robust clinical translation. 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