Srp14, a crucial protein subunit of the signal recognition particle (SRP), is essential for co-translational translocation to the endoplasmic reticulum. It forms a heterodimer with SRP9, playing a key role in 7SL RNA processing and Alu retrotransposition, and is also involved in the transcriptional regulation of 7SL and BC200 RNA [1,2]. Additionally, it participates in diverse biological processes such as the unfolded protein response, HIV-1 Tat mRNA processing, and is associated with diseases like endometriosis and idiopathic inflammatory myopathies [3,4,7].

In the context of the unfolded protein response, SRP14 reduction, which requires PRKR-like ER kinase (PERK)-mediated eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, leads to reduced translocation of fusion proteins and endogenous cathepsin D, suggesting that the PERK-SRP14 axis-mediated translocational attenuation is a protective measure for the response [3]. In HIV-1 latency, knockdown of SRP14 negatively affects tat mRNA processing, translation, and Tat-mediated transactivation, increasing latent infection, while its overexpression in resting CD4+ T-cells can reverse latency and induce virus production [5]. Regarding porcine reproductive and respiratory syndrome virus (PRRSV) infection, miR-10a downregulates SRP14 expression to inhibit viral replication, and the IRF8-miR-10a-SRP14 regulatory pathway is identified as a new antiviral strategy [6].

In conclusion, Srp14 is vital for multiple biological processes, especially those related to protein translocation and RNA regulation. Its study in various disease-related models, such as in ER stress, HIV-1 latency, and PRRSV infection, provides insights into disease mechanisms, potentially guiding the development of new treatments.