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The much-celebrated [[Isidore of Pelusium|Saint Isidore of Pelusium]] flourished in the fifth century as a great Pelusian ascetic and a defender of Orthodoxy against [[Nestorianism]]. An Amonathus is also recorded in the synaxaries as being a venerable saint from Pelusium. The last known bishop before the Islamic invasion that would occur 100 years later was George, a disciple of [[Sabbas the Sanctified|Saint Sabbas]] under [[Zoilus of Alexandria|Patriarch Zoilus]] (541–551). The city was later taken by the [[Miaphysitism|Miaphysites]]. The city was destroyed after the Great Schism by the Latin Church, and the see of Pelusium remained a titular diocese.
The modern Archdiocese of Pelusium was founded in 1908 together with the archdioceses of [[Archdiocese of Ptolemais|Ptolemais]], [[Archdiocese of Aksum|Aksum]], [[Archdiocese of Leontopolis|Leontopolis]] and [[Archdiocese of Nubia|Nubia]]. It's first archbishop, Amphilochios, was ordained in 1914. Its seat is located in the city of Port Said, the nearest inhabited land from Pelusium, thirty kilometers northwest.