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The study of PTMs has profoundly broadened the scope of therapeutic target discovery. Building upon the success of PROTACs, this heterobifunctional paradigm has expanded beyond ubiquitination to recruit diverse endogenous enzymes for proximity\u2010induced PTM modulation (e.g., PHICS, AceTACs, and DUBTACs). As a powerful complement, direct chemical editing via monovalent small molecules achieves autonomous, enzyme\u2010independent PTM writing by leveraging inherent chemical reactivity and ligand\u2010directed proximity. Crucially, this strategy extends to broader bioconjugation methods, enabling the installation of PTM mimetics and precise editing of the protein backbone. By synthesizing advances in induced proximity and direct chemical writing, this review provides a framework for developing next\u2010generation precision therapeutics that dynamically edit the PTM landscape.<\/jats:p>","DOI":"10.1002\/chem.71737","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:40:21Z","timestamp":1790826021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BeyondTACs: Chemical Editing of Posttranslational Modifications (PTMs) for Therapeutic Intervention"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6708-9833","authenticated-orcid":false,"given":"Chen","family":"Zhang","sequence":"first","affiliation":[{"name":"Center of Drug Discovery, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P.R. 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