A recent study identified two ubiquitylation sites on CD47 that are distinct from the putative sites mentioned above and showed that in human glioma cells, activated EGFR enhanced Src-mediated CD47 Y288 phosphorylation, which blocked binding of the E3 ubiquitin ligase TRIM21 to CD47 and prevented TRIM21-mediated CD47 K99/102 polyubiquitylation and CD47 degradation, resulting in increased CD47 protein levels, which led to inhibition of phagocytosis by tumor-infiltrating macrophages and ultimately facilitated tumor immune escape (48). Here, TRIM21 is linked to central nervous system cancer.