MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation [1,3]. The Mediator complex usually cooperates with transcription factors to participate in RNA polymerase II-mediated gene transcription [2]. Genetic models, such as gene knockout mouse models, can be used to study the function of MED27.

In cardiac development, ablation of MED27 in developing mouse cardiomyocytes leads to embryonic lethality, while its deletion in adult cardiomyocytes causes heart failure and mortality. This reveals that MED27 is essential for cardiac development and function by maintaining the stability of the Mediator core [6].

In breast cancer, MED27 knockdown in triple-negative breast cancer cells inhibits cancer cell metastasis and stemness maintenance, and also sensitizes breast cancer cells to epirubicin treatment. Mechanistically, MED27 transcriptionally regulates KLF4 by binding to its promoter region [2].

In melanoma, silencing of MED27 leads to melanoma cell proliferation inhibition, cell cycle arrest, and apoptosis induction, along with inactivation of PI3K/AKT and MAPK/ERK signaling and activation of the apoptotic pathway [4].

In adrenal cortical carcinoma, down-regulation of MED27 induces cell apoptosis and attenuates cell proliferation, invasion, and metastasis, regulating the expression of EMT-related proteins and Wnt/β-catenin signaling pathway-related proteins [5].

In neurodevelopmental disorders, biallelic MED27 variants lead to a broad phenotypic continuum from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. Features include global developmental delay/intellectual disability, bilateral cataracts, infantile hypotonia, microcephaly, gait ataxia, dystonia, and more. Brain MRI shows cerebellar atrophy, white matter volume loss, pontine hypoplasia, etc. [1,3].

In conclusion, MED27 is crucial for maintaining the stability of the Mediator complex, thus playing essential roles in cardiac development and function. In diseases, it promotes the progression of certain cancers like breast cancer, melanoma, and adrenal cortical carcinoma, and is associated with neurodevelopmental disorders. The study of MED27 using gene knockout models has provided valuable insights into its functions in these biological processes and disease conditions.