SETD1B, also known as lysine-specific methyltransferase, is crucial for depositing H3K4 methyl marks, assisting in transcriptional activation of genes. It is involved in multiple biological processes such as embryonic development, hematopoiesis, spermatid development, and is implicated in various diseases [2,6].

Pathogenic variants in SETD1B are associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, seizures, and autism [1,4,5,7]. Males are more severely affected. Functional tests suggest a loss-of-function mechanism of SETD1B variants [1]. In B-cell lymphoma, SETD1B mutations confer apoptosis resistance and BCL2 independence. SETD1B acts as a tumor suppressor and its deficiency leads to resistance to certain inhibitors [3]. In hepatocellular carcinoma, high-level SETD1B gene expression is associated with unfavorable prognosis [8].

In conclusion, SETD1B is essential for gene transcriptional activation through H3K4 methylation. Its dysfunction is linked to neurodevelopmental disorders and cancers. Studies on SETD1B, especially through loss-of-function models, help us understand its role in normal biological processes and disease mechanisms, providing potential targets for diagnosis and treatment.