Rbm5, also known as LUCA-15, is an RNA-binding protein. It is involved in the regulation of alternative splicing, a crucial process for generating diverse mRNA transcripts from a single gene, and has been implicated in apoptosis and cell proliferation regulation [3,4,6]. It may be part of the U2 snRNP complex engaged with intron branch sites in pre-mRNA splicing [1].

In ALS hSOD1G93A models, up-regulation of Rbm5 increased motor neuron apoptosis by inhibiting Rac1-mediated neuroprotection, while genetic knockdown of Rbm5 rescued motor neurons from degeneration by activating Rac1 signaling [2]. In medulloblastoma, Rbm5 acts as a tumor suppressor, and its reduced expression is associated with lower overall survival. Knockdown of Rbm5 in Daoy cells induced proliferation, while overexpression repressed cell proliferation and migration, with Rbm5 regulating Wnt/β-catenin signaling [5]. In acute myeloid leukemia, Rbm5 is highly overexpressed, and its loss significantly impairs leukemia maintenance in vitro and in vivo, as it activates the oncogenic protein HOXA9 [7]. In primary mouse neurons, Rbm5 inhibition does not modify survival in traumatic or hypoxic-ischemic injury models, but it regulates intracellular responses to injury in a sex-dependent manner [8].

In conclusion, Rbm5 is a key regulator in multiple biological processes. Its functions in apoptosis, cell proliferation, and alternative splicing have significant implications for diseases such as ALS, medulloblastoma, and acute myeloid leukemia. Studies using genetic knockdown or knockout models in various disease contexts have provided valuable insights into Rbm5's role, helping to understand the underlying molecular mechanisms and potentially guiding the development of targeted therapies.