Plasma membrane-associated and intracellular proteins and protein complexes play a pivotal role in pathogen recognition and disease resistance signaling in plants and animals. Leaf rust is one of the most prevalent and most devastating wheat diseases. Here, we cloned the major race-specific leaf rust resistance gene Lr14a
from hexaploid wheat. The Lr14a
was found to encode a membrane-localized protein containing twelve ankyrin repeats that possibly acts as a non-selective, Ca2+-permeable cation channel to mediate the resistance. This study forms the basis to explore ANK-TM-like genes in disease resistance breeding.