Iron-sulfur (Fe-S) clusters are ubiquitous in all life forms and are among the most ancient, structurally diverse prosthetic groups. They play critical and versatile roles as electron transport units, catalytic centers, structural units, or regulators in numerous biological pathways. The ubiquitous 4Fe-4S clusters, assembled from high-spin Fe2+ and Fe3+ ions, can exist in four oxidation states: [4Fe-4S]0,1+,2+,3+. Typically, 4Fe-4S clusters exhibit only one redox pair when acting as electron transport units in physiological processes, either [4Fe-4S]1+/2+ or [4Fe-4S]2+/3+, with common spin states of S = 0 for [4Fe-4S]2+ and S = 1/2 for [4Fe-4S]1+/3+. In contrast, the 4Fe-4S clusters in ferredoxin:thioredoxin reductase family exhibit three oxidation states, [4Fe-4S]1+/2+/3+, allowing these clusters to provide two electrons to cleave an adjacent disulfide bond. Notably, in group 4 ferredoxin: thioredoxin reductase (AFTR), an unusual enzymatic [4Fe-4S]+ intermediate with a spin state of S = 7/2 has been observed. Here, we report the first comprehensive spectroscopic and computational investigation of S = 7/2 [4Fe-4S]+ species. Our results suggest that the S = 7/2 ground state in the enzymatic cluster and in the synthetic cluster is stabilized via a cluster core modification, i.e., protonation on one of the bridging sulfides. Our studies reveal a unique mechanism for AFTR where the enzymatic 4Fe-4S cluster serves as a proton coupled electron transfer unit in the disulfide reduction chemistry. Our finding expands the scope of Fe-S chemistry, providing the first direct evidence that Fe-S clusters can mediate proton transfer, a function that may have broader implications for Fe-S clusters in enzymes.