Regulating the transcription, translation and secretion of cytokines is crucial for controlling the appropriate balance of inflammation. We recently reported that the sorting receptor Sortilin interacts with various cytokines and is involved in the exocytic trafficking of IFN-α in plasmacytoid dendritic cells (pDCs) (Yabe-Wada T et al. Sci. Rep. 6, 26566 (2016)). SPR analysis with recombinant proteins revealed interactions of Sortilin with IFN-α, IL-10, IL-12 and IL-17A as well as with two known ligands, IFN-γ and IL-6. Sortilin depletion in pDCs led to a reduction of IFN-α secretion, and microscopic imaging revealed the co-localization of Sortilin with IFN-α, whereas IFNA gene transcription in response to TLR stimulation was unaffected by Sortilin knockdown. These results suggest that Sortilin plays a pivotal role in the exocytic trafficking of IFN-α in pDCs. Moreover, we observed that sortilin mRNA was degraded posttranscriptionally upon stimulation with various TLR ligands. Interestingly, Sortilin mRNA possessed a C-rich element (CRE) in the 3’ UTR region, which acted as a cis-element and was recognized by poly-rC-binding proteins (PCBPs). We previously demonstrated that depletion of PCBP1 with siRNA enhanced the degradation of Sortilin transcripts. In addition, we found that depletion of PCBP2, a paralog of PCBP1, also facilitated the degradation of Sortilin transcripts. RNA immunoprecipitation revealed direct interaction of PCBP2 as well as PCBP1 with the 3’ UTR of Sortilin mRNA, suggesting that PCBP1 and PCBP2 can act as a trans-acting factor to stabilize Sortilin mRNA. An in vitro band shift assay revealed that the nucleotide-binding ability of PCBP2 was also impaired by zinc ions. We previously observed that Sortilin transcripts were degraded by zinc supplementation, and the zinc chelator prevented this degradation, suggesting the importance of cellular zinc status for Sortilin expression. Both PCBP1 and PCBP2 may therefore control the stability of Sortilin transcripts by sensing intracellular zinc levels.