By contrast, in prostate cancer cells, sortilin acts as a negative modulator of progranulin activity, as its overexpression reduced progranulin levels by promoting clathrin-dependent progranulin internalization and degradation, leading to a reduction in AKT activation, cell proliferation, migration, invasion and anchorage-independent growth [146,158,159] (Figure 2). The gene discussed is GRN; the disease is prostate carcinoma.