A study published in *Nature* (2014) identifies NCOA4 as a cargo receptor mediating ferritinophagy, the selective autophagic degradation of ferritin to release iron. Using quantitative proteomics, the researchers identified NCOA4 as a highly enriched protein in autophagosomes, associated with ATG8 proteins that facilitate cargo-receptor complex entry into autophagosomes. NCOA4 was found to bind ferritin heavy and light chains, components of an iron-storage complex. The study shows that NCOA4 is essential for delivering ferritin to lysosomes for degradation, which is critical for maintaining iron homeostasis. NCOA4 deficiency leads to reduced bioavailable intracellular iron, highlighting its role in iron regulation. The findings reveal NCOA4 as a selective cargo receptor for ferritinophagy, providing insights into autophagosomal cargo-receptor interactions. The study also underscores the importance of autophagy in cellular iron homeostasis and its potential role in cancer and neurodegenerative diseases. The research highlights the utility of quantitative proteomics in uncovering receptor-cargo relationships and autophagy mechanisms.A study published in *Nature* (2014) identifies NCOA4 as a cargo receptor mediating ferritinophagy, the selective autophagic degradation of ferritin to release iron. Using quantitative proteomics, the researchers identified NCOA4 as a highly enriched protein in autophagosomes, associated with ATG8 proteins that facilitate cargo-receptor complex entry into autophagosomes. NCOA4 was found to bind ferritin heavy and light chains, components of an iron-storage complex. The study shows that NCOA4 is essential for delivering ferritin to lysosomes for degradation, which is critical for maintaining iron homeostasis. NCOA4 deficiency leads to reduced bioavailable intracellular iron, highlighting its role in iron regulation. The findings reveal NCOA4 as a selective cargo receptor for ferritinophagy, providing insights into autophagosomal cargo-receptor interactions. The study also underscores the importance of autophagy in cellular iron homeostasis and its potential role in cancer and neurodegenerative diseases. The research highlights the utility of quantitative proteomics in uncovering receptor-cargo relationships and autophagy mechanisms.