Ghebrehiwet et al. (2019) provide evidence that a synthetic peptide directed to HKH-20 can inhibit HK-gC1qR binding in vitro, with the histidine residues critical for this interaction. There are unique considerations for gC1qR-directed peptide therapy for the CNS. The disulfide bonds in LyP-1, a tumor-homing peptide with gC1qR as its receptor, provide evidence of drug delivery challenges to the CNS. The disulfide linkages of LyP-1 are cleaved in the brain, hindering the targeting of glioma and metastatic brain tumors (Bickel et al., 1995). This evidence concerns the gene PTPN22 and glioma.