It later became part of the Palace and Holy Steps complex commissioned by Sixtus V in 1586. Later Pope Alexander III is mentioned as presiding here over the ceremony of the washing of the feet. Gregory IV (†844) had a private apartment built near the chapel to allow him to pray there. It formed part of the Lateran Palace, headquarters of the public offices of the papal court throughout the Middle Ages. The antiquarian Marangoni along with Onofrio Panvinio quote documents that cite the acquisition in 583 by Pope Gregory of relics from Constantinople, including an arm of St Lawrence, that were housed in the church of St Lawrence in Lateran palace. The first mention of the chapel is found in the Liber Pontificalis, during the tenure of Pope Stephen III (†772). It is located at the top of the Scala Sancta, ('Holy Stairs').

It was originally dedicated to Saint Lawrence, and served as the pope's private oratory until the Renaissance. 'the most holy things') and to the Holy of Holies in Jerusalem, traditionally called in Latin both sanctum sanctorum (the singular form) or sancta sanctorum. The spelling is Sancta, the neuter plural form of the Latin adjective 'holy': this is a reference to the multiple relics preserved there (i.e. The chapel acquired the Sancta Sanctorum sometime in the ninth century. The chapel is the only building from the old Lateran Palace that was not destroyed during its reconstruction. It was the original private chapel of the papacy before it moved to Avignon, and later to the Vatican Palace. The Sancta Sanctorum ( Italian: Chiesa di San Lorenzo in Palatio ad Sancta Sanctorum) is a Roman Catholic chapel entered via the Scala Sancta (Holy Staircase) of the Lateran Palace in Rome. Main altar of the Sancta Sanctorum, enshrining the Uronica.

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