Srsf4, a member of the serine-/arginine (SR)-rich protein family, is involved in both constitutive and alternative splicing of pre-mRNA, and plays a crucial role in RNA metabolism [2]. As an essential component of spliceosomes, it also participates in processes like spliceosome assembly, mRNA export, and nonsense-mediated mRNA decay, which are vital for maintaining cellular and tissue homeostasis [5].

Srsf4 has been linked to multiple diseases and biological processes. In glioma, its high expression is associated with histological grade, IDH1 status, 1p/19q codeletion, molecular subtype, tumor recurrence, and poor prognosis. Srsf4 promotes temozolomide (TMZ) resistance by positively regulating MDC1 and accelerating double-strand break repair, and targeting it can improve chemosensitivity [1]. In pulmonary hypertension, Srsf4 upregulates the expression of ca-circFOXP1 by splicing exons 6 and 9 of FOXP1 pre-mRNA, which then affects pulmonary arterial smooth muscle cell proliferation through the R-loop-mediated regulation of FOXP1 and SMAD2 phosphorylation [3]. In patients with a missense variant of the Srsf4 gene, lower Srsf4 protein expression leads to mitochondrial dysfunction, presenting as leukopenia, lymphopenia, and neutropenia [4].

In conclusion, Srsf4 is a key regulator in RNA splicing and metabolism, with its dysregulation contributing to various diseases such as glioma, pulmonary hypertension, and bone marrow failure. Understanding Srsf4 through functional studies, including potential gene knockout models, provides insights into disease mechanisms and may offer new therapeutic targets.