Combined with the observed negative regulation of PTEN by the C5a/C5aR axis in this study, it is proposed that this axis may cooperatively mediate PTEN downregulation through multiple pathways, particularly under inflammatory conditions characterized by signaling crosstalk and non‐coding RNA dysregulation, thereby promoting PI3K/AKT activation and the progression of LN. Here, C5 is linked to lobular neoplasia.