The Mystery of Iniquity - The man of sin revealed
Corruption of doctrine and worship came in by degrees, and the usurping of power was gradual; thus the mystery of iniquity prevailed. Superstition and idolatry were advanced by pretended devotion, and bigotry and persecution were promoted by pretended zeal for God and his glory. This mystery of iniquity was even then begun; while the apostles were yet living, persons pretended zeal for Christ, but really opposed him.
The persons are described, who are his willing subjects. Their sin is this; They did not love the truth, and therefore did not believe it; and they were pleased with false notions.
This passage exactly agrees with the system of popery, as it prevails in the Romish church, and under the Romish popes. But though the son of perdition has been revealed, though he has opposed and exalted himself above all that is called God, or that is worshipped; and has spoken and acted as if he were a god upon earth, and has proclaimed his insolent pride, and supported his delusions, by lying miracles and all kinds of frauds; still the Lord has not yet fully destroyed him with the brightness of his coming; that and other prophecies remain to be fulfilled before the end shall come ---- Matthew Henry Bible Commentary

The doctrine of justification by the works of the law was industriously spread, and zealously preached and received; all which laid the foundation, and are the life and soul of popery:  only he who now letteth, will let, until he be taken out of the way; that is, the Roman empire and Roman emperors, and which were by degrees entirely removed, and so made way for the revelation of this wicked one: and which was done partly by Constantine the emperor receiving the Christian faith, whereby the Roman empire as Pagan ceased; and by increasing the riches of the church, and feeding the pride, ambition, and covetousness of the bishops, especially the bishop of Rome; and next by removing the seat of the empire from Rome to Byzantium, which he called Constantinople: here the Greek emperors continued in succession, and neither they themselves, nor even their exarchs, resided at Rome, but at Ravenna; so that way was made for antichrist to come to his seat, and there was nothing to rival and eclipse the grandeur, power, and glory of the Roman popes: and that which let was also taken out of the way, by the division of the empire, by Theodosius, giving to his elder son Arcadius, the eastern, and to the younger, Honorius, the western parts of it: the eastern empire was in process of time seized upon and possessed by Mahomet and the Saracens; and the western empire was overrun by the Goths, Vandals, and Huns, and became extinct about the year 476, in Augustulus, the last of the Roman emperors, who was obliged to abdicate the government by Odoacer king of the Heruli; when the kingdom of the Lombards took place in Italy, and afterwards that was translated to Charles the great, king of the French; so that there was nothing more of the Roman empire remaining than the bare name, as at this day; and by this means the popes of Rome got to the height of their power and glory, which is meant by the revelation of the man of sin. ----- Gill's Exposition of the Bible