Autophagy protects cellular homeostasis by capturing cytosolic components and 
invading pathogens for lysosomal degradation. Autophagy receptors target cargo 
to autophagy by binding ATG8 on autophagosomal membranes. The expansion of the 
ATG8 family in higher eukaryotes suggests that specific interactions with 
autophagy receptors facilitate differential cargo handling. However, selective 
interactors of ATG8 orthologs are unknown. Here we show that the selectivity of 
the autophagy receptor NDP52 for LC3C is crucial for innate immunity since cells 
lacking either protein cannot protect their cytoplasm against Salmonella. LC3C 
is required for antibacterial autophagy because in its absence the remaining 
ATG8 orthologs do not support efficient antibacterial autophagy. Structural 
analysis revealed that the selectivity of NDP52 for LC3C is conferred by a 
noncanonical LIR, in which lack of an aromatic residue is balanced by 
LC3C-specific interactions. Our report illustrates that specificity in the 
interaction between autophagy receptors and autophagy machinery is of functional 
importance to execute selective autophagy.