Under homeostatic conditions, proNGF and mNGF act synergistically through TrkA/p75NTR; however, imbalances in the relative abundances of TrkA and p75NTR (or of their ligands mNGF/proNGF) have been described in multiple CNS disorders (Fahnestock et al., 2001; Tiveron et al., 2013), suggesting how tipping the scale in favor of proNGF/p75NTR signaling can lead to neurodegeneration and cell death. The gene discussed is NGFR; the disease is central nervous system disorder.