The nuclear factor (NF)-κB essential modulator (NEMO) is a key regulator in NF-κB-mediated signaling. By transmitting extracellular or intracellular signals, NEMO can control NF-κB-regulated genes. NEMO dysfunction is associated with inherited diseases such as incontinentia pigmenti (IP), ectodermal dysplasia, anhidrotic, with immunodeficiency (EDA-ID), and some cancers. We focus on molecular studies, human case reports, and mouse models emphasizing the significance of NEMO molecular interactions and modifications in health and diseases. This knowledge opens new opportunities to engineer suitable drugs that may putatively target precise NEMO functions attributable to various diseases, while leaving other functions intact, and eliminating cytotoxicity. Indeed, with the advent of novel gene editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9, treating some inherited diseases may in the long run, become a reality.

核因子（NF）-κB必需调节剂（NEMO）是NF-κB介导的信号传导中的关键调节剂。通过传递细胞外或细胞内信号，NEMO可以控制NF-κB调控的基因。NEMO功能障碍与遗传性疾病有关，如色素失禁（IP），外胚层发育不良，无汗，免疫缺陷（EDA-ID）和某些癌症。我们专注于分子研究，人类病例报告和小鼠模型，强调了NEMO分子相互作用和修饰在健康和疾病中的重要性。这些知识为设计合适的药物开辟了新的机会，这些药物可能针对多种疾病导致的精确NEMO功能，而其他功能保持不变，并消除了细胞毒性。确实，