核受体结合SET域蛋白（NSDs）利用S-腺苷基-L-甲硫氨酸（SAM）作为甲基供体，催化组蛋白3赖氨酸36位点的单甲基化或双甲基化（H3K36me1和H3K36me2）。作为NSD蛋白家族的关键成员，NSD2在多种疾病的发病机制和进展中发挥重要作用，例如癌症、炎症和传染性疾病，并可作为一种有前景的药物靶点。开发有效且特异性的NSD2抑制剂可能为潜在的新疗法提供可能性。虽然目前NSD2抑制剂和降解剂仍处于早期药物开发阶段，但令人振奋的是，一种选择性NSD2抑制剂KTX-1001已进入临床试验。本文综述了NSD2的结构和功能、其在各种人类疾病中的作用，以及针对NSD2的药物发现策略的最新进展。同时还讨论了发展NSD2抑制剂和降解剂面临的挑战、机遇和未来发展方向。

Nuclear receptor binding SET domain proteins (NSDs) catalyze the mono- or dimethylation of histone 3 lysine 36 (H3K36me1 and H3K36me2), using S-adenosyl-l-methionine (SAM) as a methyl donor. As a key member of the NSD family of proteins, NSD2 plays an important role in the pathogenesis and progression of various diseases such as cancers, inflammations, and infectious diseases, serving as a promising drug target. Developing potent and specific NSD2 inhibitors may provide potential novel therapeutics. Several NSD2 inhibitors and degraders have been discovered while remaining in the early stage of drug development. Excitingly, KTX-1001, a selective NSD2 inhibitor, has entered clinical trials. In this Perspective, the structures and functions of NSD2, its roles in various human diseases, and the recent advances in drug discovery strategies targeting NSD2 have been summarized. The challenges, opportunities, and future directions for developing NSD2 inhibitors and degraders are also discussed.