If I understand right, your protocol question is aiming at the data link layer. It involves frame structure, frame sync and error detection.
In part, the protocol decision depends on your communication structure, e.g. if packets of constant size are transmitted with fixed rate or some kind of adressing or variable packet structure is intended. A simple option is to divide down the clock to make it act as frame/word sync. An unique sync word would be required in addition to mark a packet boundary.
As a side remark, in the lower data rate domain up to 100 or possibly 200 MBPS, data links can also work over a single differential pair for each direction, using asynchronous or synchronous serial transmission and oversampling at the RX side. Combined with 8b/10b coding, also ethernet-like transformer coupled physical layers can be used.