Rnasek, also known as ribonuclease kappa, is a highly conserved transmembrane protein. It is a component of the V-ATPase complex, playing a crucial role in processes like lysosomal hydrolase delivery, autophagosome degradation [1], endocytosis [3], and is associated with the replication of multiple viruses [3,4,6]. It may also be involved in the pathogenesis of periodontitis [5].

In autophagy, Rnasek knockout cells show disrupted cargo degradation in autolysosomes despite intact autophagosome maturation, indicating its role in the final degradation step [1]. Knockdown of Rnasek leads to reduced levels of a subset of hydrolases in lysosome fractions, and knockdown of PLD3 (affected by Rnasek depletion) causes a defect in autophagosome clearance [1]. In viral infections, RNAi-mediated depletion of Rnasek in human cells blocks the internalization of diverse acid-dependent viruses that enter from endosomal compartments, without affecting general endocytic uptake of transferrin [4]. Knockdown of Rnasek also reduces the replication of viruses like PEDV [2], DENV [6], HRV, influenza A virus, and dengue virus [3].

In conclusion, Rnasek is essential for lysosomal function, autophagosome degradation, and the entry and replication of certain viruses. Gene knockout studies have revealed its significance in these biological processes, potentially providing insights into diseases related to autophagy dysfunction and viral infections.